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Genetic alterations in primary melanoma in Taiwan
Author(s) -
Sheen Y.S.,
Tan K.T.,
Tse K.P.,
Liao Y.H.,
Lin M.H.,
Chen J.S.,
Liau J.Y.,
Tseng Y.J.,
Lee C.H.,
Hong C.H.,
Liao J.B.,
Chang H.T.,
Chu C.Y.
Publication year - 2020
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.18425
Subject(s) - primary (astronomy) , medicine , melanoma , dermatology , oncology , biology , genetics , cancer research , physics , astronomy
Summary Background Acral melanoma ( AM ) is the most common histopathological subtype of malignant melanoma in Asians. However, differences in the mutational profiles underlying AM and nonacral cutaneous melanoma ( NAM ) in Asians are not well understood. Objectives To augment the understanding of the prevalence, patterns and associations of various mutations between different subtypes of melanoma. Methods We performed comprehensive genomic profiling of 409 cancer‐associated genes, using next‐generation sequencing, in 66 primary melanomas comprised of 45 AM s and 21 NAM s. Results Most of the AM s ( n = 27/45; 60%), but only five of 21 (24%) NAM s, were triple wild‐type (triple‐ WT ) tumours. Compared with AM s, NAM s exhibited a significantly higher frequency of BRAF mutations. The frequencies of NRAS / KRAS mutations, cell‐cycle aberrations, copy number gains in BIRC 2 , BIRC 3 and BIRC 5 , and gains of receptor tyrosine kinase genes were significantly higher in AM s. Ulceration was found at significantly higher rates in the AM s and NAM s with cell‐cycle aberrations and gains of receptor tyrosine kinase genes. Notably, cell‐cycle aberrations and copy number gains in BIRC 2 , BIRC 3 and BIRC 5 were significantly associated with poor melanoma‐specific survival in the 66 patients with melanoma and especially in the 45 patients with AM . Multivariate analysis showed that lymph node metastasis and cell‐cycle aberrations were independent prognostic factors of melanoma‐specific survival. Conclusions This study strengthens our understanding of the patterns and clinical associations of oncogenic mutations in AM s and NAM s in Asians.What's already known about this topic?Mutation frequencies of driver genes vary between melanoma subtypes. Acral melanoma is the most common subtype of melanoma in Asians. KIT mutations and copy number variations occur more frequently in the acral subtype of melanoma than in the nonacral subtypeWhat does this study add?NRAS/KRAS mutations, cell‐cycle aberrations, copy number gains in BIRC2 , BIRC3 and BIRC5 , and amplifications of receptor tyrosine kinase genes were significantly enriched in acral melanoma and could be potential targets for treatment. Melanomas with cell‐cycle aberrations and gains in receptor tyrosine kinase genes were significantly more likely to contain ulceration.What is the translational message?Cell‐cycle aberrations and copy number gains in BIRC2 , BIRC3 and BIRC5 were significantly associated with poor melanoma‐specific survival. These observations should be explored further for future drug development.